Signaling by C-reactive protein (CRP) and IgG receptors (Fc receptors)
CRP is an acute phase reactant that is elevated under inflammatory conditions and with obesity. Chronic elevations in circulating CRP are an important risk factor for cardiovascular disease. We recently discovered that CRP prevent eNOS activation and normal endothelial function via binding to FcγRIIB, which is an inhibitory IgG receptor that we have discovered is expressed in endothelial cells. Studies of CRP transgenic mice further indicated that CRP causes hypertension by modifying vascular angiotensin II receptor expression, and that CRP disrupts intimal layer integrity. These mechanisms provide novel causal linkage between inflammation and obesity and vascular disease, and their molecular underpinnings and implications are under study. The ultimate goal is to determine if CRP/FcγRIIB actions in endothelium can be blocked to prevent or treat cardiovascular disease.